tbuckley/cabot-search huggingface dataset:
Quartet protein reference materials and datasets for multi-platform assessment of label-free proteomics
Authors: Sha Tian, Dongdong Zhan, Ying Yu, Yunzhi Wang, Mingwei Liu, Subei Tan, Yan Li, Lei Song, Zhaoyu Qin, Xianju Li, Yang Liu, Yao Li, Shuhui Ji, Shanshan Wang, Zhaoyu Qin, Qingyu He, Xingfeng Yin, Lunzhi Dai, Haiteng Deng, Chao Peng, Ping Wu, Minjia Tan, Jing Jiang, Yaoyang Zhang, Yunxia Li, Wenqin Liu, Wei Chen, Rui Wang, Jin Zi, Qidan Li, Mingzhou Bai, Zeng Wang, Zhanlong Mei, Zhongyi Cheng, Jun Zhu, Xuemei Wu, Xing Yang, Yue Zhou, Yuanting Zheng, Fuchu He, Jun Qin, Chen Ding
Journal: Genome biology (2023)

Quantitative proteomics is an indispensable tool in life science research. However, there is a lack of reference materials for evaluating the reproducibility of label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based measurements among different instruments and laboratories.Here, we develop the Quartet standard as a proteome reference material with built-in truths, and distribute the same aliquots to 15 laboratories with nine conventional LC-MS/MS platforms across six cities in China. Relative abundance of over 12,000 proteins on 816 mass spectrometry files are obtained and compared for reproducibility among the instruments and laboratories to ultimately generate proteomics benchmark datasets. There is a wide dynamic range of proteomes spanning about 7 orders of magnitude, and the injection order has marked effects on quantitative instead of qualitative characteristics.Overall, the Quartet offers valuable standard materials and data resources for improving the quality control of proteomic analyses as well as the reproducibility and reliability of research findings.
Electrolyte Disorders in Mitochondrial Cytopathies: A Systematic Review
Authors: Daan H.H.M. Viering, Lars Vermeltfoort, René J.M. Bindels, Jaap Deinum, Jeroen H.F. de Baaij
Journal: Journal of the American Society of Nephrology (2023)

Several recent studies identified mitochondrial mutations in patients with Gitelman or Fanconi syndrome. Mitochondrial cytopathies are generally not considered in the diagnostic workup of patients with electrolyte disorders. In this systematic review, we investigated the presence of electrolyte disorders in patients with mitochondrial cytopathies to determine the relevance of mitochondrial mutation screening in this population. Our analysis demonstrates that electrolyte disorders are commonly reported in mitochondrial cytopathies, often as presenting symptoms. Consequently, more clinical attention should be raised for mitochondrial disease as cause for disturbances in electrolyte homeostasis. Further prospective cohort studies are required to determine the exact prevalence of electrolyte disorders in mitochondrial cytopathies.
It’s All in the Timing
Authors: Alexander J. Beagle, Bernie Y. Sunwoo, Rebecca L. Olin, Brian S. Schwartz, Brian L. Block
Journal: New England Journal of Medicine (2023)

A 55-year-old man with acute myeloid leukemia began to have shortness of breath, cough with blood-tinged sputum, and hypoxemia 17 days after receiving a myeloablative allogeneic stem-cell transplant from a haploidentical donor.
Immunization with Attenuated Pneumococcal Strains Provides Protection against Pneumococcal Colonization in Humans
Authors: Ana Rita Narciso, Birgitta Henriques-Normark
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Immunization with Attenuated Pneumococcal Strains Provides Protection Against Pneumococcal Colonization in Humans." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Next Chapter for Weight Control — Small-Molecule GLP-1 Receptor Agonists?
Authors: E. Dale Abel
Journal: New England Journal of Medicine (2023)

Obesity is a major risk factor for many health conditions, including cardiovascular disease, type 2 diabetes, sleep apnea, and cancer. The therapeutic armamentarium for long-term weight management is limited by side effects and contraindications.1 Two injectable incretin-based glucagon-like peptide-1 (GLP-1) receptor agonists — liraglutide (3.0 mg daily) and semaglutide (2.4 mg weekly) — have been approved by the Food and Drug Administration (FDA) for weight management, with better side-effect profiles than other treatments. An oral formulation of semaglutide (7 or 14 mg once daily) has been approved by the FDA for the treatment of type 2 diabetes but not yet . . .
Second primary malignancies in patients with lymphoma in Denmark after high-dose chemotherapy and autologous haematopoietic stem-cell transplantation: a population-based, retrospective cohort study
Authors: Trine Trab, Joachim Baech, Lasse Hjort Jakobsen, Simon Husby, Marianne Tang Severinsen, Sandra Eloranta, Jette S Gørløv, Judit M Jørgensen, Sif Gudbrandsdottir, Thomas Stauffer Larsen, Peter Brown, Kirsten Grønbæk, Karin E Smedby, Tarec C El-Galaly
Journal: The Lancet Haematology (2023)
Real-World Impact of Prophylactic Growth Factor Use on Timing of Febrile Neutropenia and Infection After High-Risk Chemotherapy
Authors: Douglas W. Blayney, Nicole M. Kuderer, Alice Kate Cummings Joyner, John Jarvis, Dominic Nunag, Jasmine Wells, Lan Huang, Ramon Monhanlal, Gary H. Lyman
Journal: Journal of the National Comprehensive Cancer Network (2023)

Background: Prophylactic growth-factor therapy with granulocyte colony-stimulating factor (G-CSF) reduces the risk of febrile neutropenia (FN) in patients with breast cancer initiating myelosuppressive chemotherapy. However, little is known about the protective benefit early in the chemotherapy cycle. Methods: To assess the relationship between G-CSF prophylaxis and incidence of FN/infection in week 1 versus beyond week 1 of the first chemotherapy cycle, a retrospective study was conducted using Medicare claims from 2005 through 2020 among patients with breast cancer initiating high-risk chemotherapy. Two cohorts were compared based on G-CSF prophylaxis within 3 days following chemotherapy initiation. The primary outcome was FN or infection, defined as hospitalization with neutropenia, fever, or infection diagnosis. Secondary outcomes were a stricter definition of FN and infection-related hospitalization. Unadjusted and regression-adjusted proportions of patients experiencing each outcome during week 1 versus beyond week 1 of the first chemotherapy cycle were compared. Results: Of 78,810 patients meeting all inclusion criteria (&gt;98% female; mean age, 69 years), 79% initiated TC (docetaxel/cyclophosphamide), 14% TCH (docetaxel/carboplatin/trastuzumab), and 7% TAC (docetaxel/doxorubicin/cyclophosphamide). Among patients receiving G-CSF (74%), incidence of first-cycle FN/infection was lower compared with patients not receiving G-CSF (overall, 6% vs 13%; TAC, 12% vs 19%; TC, 6% vs 12%; TCH, 5% vs 15%). However, patients who received G-CSF were generally more likely to experience FN/infection in week 1 (adjusted odds ratio [aOR], 1.24 for all; 1.73 for TAC; 1.35 for TC; and 0.76 for TCH). Results were similar for strictly defined FN (overall aOR, 1.29 for week 1 and 0.12 for beyond week 1) and infection-related hospitalization (overall aOR, 1.33 for week 1 and 0.27 for beyond week 1). Conclusions: Overall, the rates of chemotherapy-related FN and infection in week 1 of the first chemotherapy cycle are similar for patients receiving and not receiving G-CSF, suggesting continued risk in week 1 despite prophylactic G-CSF.
Articular Cartilage Regeneration via Induced Chondrocyte Autophagy by Sustained Release of Leptin Inhibitor from Thermo‐Sensitive Hydrogel through STAT3/REDD1/mTORC1 Cascade
Authors: Zhongming Huang, Chen Liu, Guangping Zheng, Liang Zhang, Qiang Zhong, Yun Zhang, Weicheng Zhao, Yiying Qi
Journal: Advanced Healthcare Materials (2023)

The pathophysiology of osteoarthritis (OA) is closely linked to autophagy abnormalities in articular chondrocytes, the sole mature cell type in healthy cartilage. Nevertheless, the precise molecular mechanism remains uncertain. Previous research has demonstrated that leptin activates mTORC1 , thereby inhibiting chondrocyte autophagy during the progression of OA. In this study, it is demonstrated that the presence of leptin induces a substantial increase in the expression of STAT3, leading to a notable decrease in REDD1 expression and subsequent phosphorylation of p70S6K, a recognized downstream effector of mTORC1. Conversely, inhibition of leptin yields contrasting effects. Additionally, the potential advantages of utilizing a sustained intra-articular release of a leptin inhibitor (LI) via an injectable, thermosensitive poly(D,L-lactide)-poly(ethylene glycol)-poly(D,L-lactide) (PDLLA-PEG-PDLLA: PLEL) hydrogel delivery system for the purpose of investigating its impact on cartilage repair are explored. The study conducted on LI-loaded PLEL (PLEL@LI) demonstrates remarkable efficacy in inhibiting OA and displays encouraging therapeutic advantages in the restoration of subchondral bone and cartilage. These findings establish a solid foundation for the advancement of a pioneering treatment approach utilizing PLEL@LI for OA.
Rechallenge With Switching Immune Checkpoint Inhibitors Following Autoimmune Myocarditis in a Patient With Lynch Syndrome
Authors: Cody Eslinger, Daniel Walden, Timothy Barry, Shimoli Shah, Niloy Jewel Samadder, Tanios S. Bekaii-Saab
Journal: Journal of the National Comprehensive Cancer Network (2023)

Immune checkpoint inhibitors (ICIs) induce profound benefits in cancer patients with mismatch repair gene mutations or high levels of microsatellite instability. Herein, we present a case of a patient with history of Muir-Torre/Lynch syndrome and metastatic gastric adenocarcinoma in the presence of an MSH2 gene mutation. The patient was initially treated with a PD-1 inhibitor, pembrolizumab, but developed grade 4 myocarditis requiring treatment with infliximab and a prolonged steroid taper. Following discontinuation of pembrolizumab, surveillance testing showed no radiographic or endoscopic evidence of progression for 7 months, until biopsy results from a repeat upper endoscopy indicated local disease recurrence. The patient was subsequently rechallenged with another PD-1 inhibitor, nivolumab, at a 50% dose reduction without recurrent adverse events and eventually achieved a complete response after 13 cycles. This case highlights the relative importance of considering careful rechallenge with ICI therapy in patients with microsatellite instability–high malignancies and a high risk of severe adverse events.
Impact of Muscle Measures on Outcome in Patients Receiving Endocrine Therapy for Metastatic Breast Cancer: Analysis of ECOG-ACRIN E2112
Authors: Tarah J. Ballinger, Helga S. Marques, Gloria Xue, Richard Hoffman, Constantine Gatsonis, Fengmin Zhao, Kathy D. Miller, Joseph Sparano, Roisin M. Connolly
Journal: Journal of the National Comprehensive Cancer Network (2023)

Background: Observational data investigating the relationship between body habitus and outcomes in breast cancer have been variable and inconsistent, largely centered in the curative setting and focused on weight-based metrics. This study evaluated the impact of muscle measures on outcomes in patients with metastatic breast cancer receiving endocrine-based therapy. Methods: Baseline CT scans were collected from ECOG-ACRIN E2112, a randomized phase III placebo-controlled study of exemestane with or without entinostat. A CT cross-sectional image at the L3 level was extracted to obtain skeletal muscle mass and attenuation. Low muscle mass (LMM) was defined as skeletal muscle index &lt;41 cm 2 /m 2 and low muscle attenuation (LMA) as muscle density &lt;25 HU or &lt;33 HU if overweight/obese by body mass index (BMI). Multivariable Cox proportional hazard models determined the association between LMM or LMA and progression-free survival (PFS) and overall survival (OS). Correlations between LMM, LMA, and patient-reported outcomes were determined using 2-sample t tests. Results: Analyzable CT scans and follow-up data were available for 540 of 608 patients. LMM was present in 39% (n=212) of patients and LMA in 56% (n=301). Those with LMA were more likely to have obesity and worse performance status. LMM was not associated with survival (PFS hazard ratio [HR]: 1.13, P =.23; OS HR: 1.05, P =.68), nor was LMA (PFS HR: 1.01, P =.93; OS HR: 1.00, P =.99). BMI was not associated with survival. LMA, but not LMM, was associated with increased frequency of patient-reported muscle aches. Conclusions: Both low muscle mass and density are prevalent in patients with hormone receptor–positive metastatic breast cancer. Muscle measures correlated with obesity and performance status; however, neither muscle mass nor attenuation were associated with prognosis. Further work is needed to refine body composition measurements and select optimal cutoffs with meaningful endpoints in specific breast cancer populations, particularly those living with metastatic disease.
Atezolizumab for Advanced Alveolar Soft Part Sarcoma
Authors: Alice P. Chen, Elad Sharon, Geraldine O’Sullivan-Coyne, Nancy Moore, Jared C. Foster, James S. Hu, Brian A. Van Tine, Anthony P. Conley, William L. Read, Richard F. Riedel, Melissa A. Burgess, John Glod, Elizabeth J. Davis, Priscilla Merriam, Abdul R. Naqash, Kristin K. Fino, Brandon L. Miller, Deborah F. Wilsker, Asma Begum, Katherine V. Ferry-Galow, Hari A. Deshpande, Gary K. Schwartz, Brian H. Ladle, Scott H. Okuno, Jill C. Beck, James L. Chen, Naoko Takebe, Laura K. Fogli, Christina L. Rosenberger, Ralph E. Parchment, James H. Doroshow
Journal: New England Journal of Medicine (2023)

Alveolar soft part sarcoma (ASPS) is a rare soft-tissue sarcoma with a poor prognosis and no established therapy. Recently, encouraging responses to immune checkpoint inhibitors have been reported.
Treatment of walled-off necrosis using lumen-apposing metal stents versus plastic stents: a systematic review and meta-analysis of data from randomized trials
Authors: Ji Young Bang, Charles Melbern Wilcox, Udayakumar Navaneethan, Robert Holbrook Hawes, Shyam Varadarajulu
Journal: Endoscopy (2023)

Abstract Background Walled-off necrosis (WON) is highly morbid disease most effectively managed by endoscopic drainage with lumen-apposing metal stents (LAMSs) or plastic stents, with or without necrosectomy. This meta-analysis compared the clinical outcomes of patients included in randomized trials treated using LAMSs or plastic stents. Methods The MEDLINE and EMBASE databases were searched to identify all data collected from randomized trials comparing LAMSs and plastic stents for the treatment of WON. The primary outcome measure was need for endoscopic necrosectomy. Results Three studies comprising 206 patients met inclusion criteria. Except for procedure duration, which was significantly shorter for LAMSs (standardized mean difference [SMD] −1.22, 95%CI −1.64 to −0.79), there was no significant difference in need for necrosectomy (38.5% vs. 41.2%; risk ratio [RR] 1.07, 95%CI 0.79–1.45), number of interventions (SMD −0.09, 95%CI −0.40 to 0.22), treatment success (90.7% vs. 94.5%; RR 0.96, 95%CI 0.87–1.06), recurrence (4.6% vs. 0.6%; RR 3.73, 95%CI 0.42–33.0), readmission (42.6% vs. 50.2%; RR 0.84, 95%CI 0.62–1.14), length of hospitalization (SMD −0.06, 95%CI −0.55 to 0.43), mortality (8.5% vs. 9.8%; RR 0.70, 95%CI 0.30–1.66), new-onset organ failure (10.6% vs. 14.6%; RR 0.72, 95%CI 0.16–3.32), bleeding (11.0% vs. 10.7%; RR 1.09, 95%CI 0.34–3.44), procedural adverse events (23.6% vs. 19.2%; RR 1.38, 95%CI 0.82–2.33), or overall costs (SMD −0.04, 95%CI −0.31 to 0.24) between LAMSs and plastic stents, respectively. Conclusions Except for procedure duration, there is no significant difference in clinical outcomes for patients with WON treated using LAMSs or plastic stents.
Achieving Normoglycemia With Tirzepatide: Analysis of SURPASS 1–4 Trials
Authors: Julio Rosenstock, Luis Vázquez, Stefano Del Prato, Denise Reis Franco, Govinda Weerakkody, Biyue Dai, Laura Fernández Landó, Brandon K. Bergman, Angel Rodríguez
Journal: Diabetes Care (2023)

OBJECTIVE Tirzepatide is a novel single-molecule glucose-dependent insulinotropic polypeptide/glucagon-like peptide 1 receptor agonist, which demonstrated unprecedented improvements in glycemic control and body weight reduction, in the SURPASS phase 3 program. In this exploratory analysis, we aimed to characterize tirzepatide-treated participants who achieved HbA1c &amp;lt;5.7% and evaluate changes in clinical markers associated with long-term cardiometabolic health. RESEARCH DESIGN AND METHODS Baseline characteristics and change from baseline to week 40 for several efficacy and safety parameters were analyzed according to HbA1c attainment category (&amp;lt;5.7%, 5.7–6.5%, and &amp;gt;6.5%) using descriptive statistics in participants taking ≥75% of treatment doses, without rescue medication, in the SURPASS 1–4 trials (N = 3,229). Logistic regression models with tirzepatide doses adjusted as a covariate were used to obtain odds ratios and assess the impact of patient characteristics achieving an HbA1c &amp;lt;5.7%. RESULTS Tirzepatide-treated participants who achieved HbA1c &amp;lt;5.7% were slightly younger, with a shorter duration of diabetes and lower HbA1c value at baseline compared with those who did not achieve HbA1c &amp;lt;5.7%. In addition, they showed greater improvements in HbA1c, body weight, waist circumference, blood pressure, liver enzymes, and lipid parameters without increasing hypoglycemia risk. CONCLUSIONS Normoglycemia was unprecedently achieved in a significant proportion of participants in the SURPASS clinical program, without increasing hypoglycemia risk, and was associated with an overall improvement in metabolic health.
Recommendations for the use of pediatric data in artificial intelligence and machine learning ACCEPT-AI
Authors: V. Muralidharan, A. Burgart, R. Daneshjou, S. Rose
Journal: npj Digital Medicine (2023)

Abstract ACCEPT-AI is a framework of recommendations for the safe inclusion of pediatric data in artificial intelligence and machine learning (AI/ML) research. It has been built on fundamental ethical principles of pediatric and AI research and incorporates age, consent, assent, communication, equity, protection of data, and technological considerations. ACCEPT-AI has been designed to guide researchers, clinicians, regulators, and policymakers and can be utilized as an independent tool, or adjunctively to existing AI/ML guidelines.
Anxiety and Risk Perception in Parents of Children Identified by Population Screening as High Risk for Type 1 Diabetes
Authors: Holly K. O’Donnell, Cristy Geno Rasmussen, Fran Dong, Kimber M. Simmons, Andrea K. Steck, Brigitte I. Frohnert, Kimberly Bautista, Marian J. Rewers, Judith Baxter, Marian J. Rewers, Kimberly Bautista, Judith Baxter, Daniel Felipe-Morales, Fran Dong, Kimberly Driscoll, Brigitte I. Frohnert, Cristy Geno Rasmussen, Patricia Gesualdo, Michelle Hoffman, Rachel Karban, Holly K. O’Donnell, Meghan Pauley, Flor Sepulveda, Crystal Silva, Kimber M. Simmons, Andrea K. Steck, Iman Taki, Kathleen Waugh, Xiaofan Jia, Liping Yu, Edwin Liu, Marisa Stahl, R. Brett McQueen, Jill M. Norris, Holly Frost, Sonja O’Leary, Martha Middlemist
Journal: Diabetes Care (2023)

To assess anxiety and risk perception among parents whose children screened positive for islet autoantibodies, indicating elevated risk for type 1 diabetes (T1D).The Autoimmunity Screening for Kids (ASK) study identified 319 children age 1 to 17 years at risk for T1D via screening for islet autoantibodies; 280 children with confirmed islet autoantibodies and their caregivers enrolled in a follow-up education and monitoring program to prevent diabetic ketoacidosis at diagnosis. Parents completed questionnaires at each monitoring visit, including a 6-item version of the State Anxiety Inventory (SAI), to assess anxiety about their child developing T1D, and a single question to assess risk perception.At the first ASK follow-up monitoring visit, mean parental anxiety was elevated above the clinical cutoff of 40 (SAI 46.1 ± 11.2). At the second follow-up monitoring visit (i.e., visit 2), mean anxiety remained elevated but started to trend down. Approximately half (48.9%) of parents reported their child was at increased risk for T1D at the initial follow-up monitoring visit (visit 1). Parents of children with more than one islet autoantibody and a first-degree relative with T1D were more likely to report their child was at increased risk.Most parents of autoantibody-positive children have high anxiety about their child developing T1D. Information about the risk of developing T1D is difficult to convey, as evidenced by the wide range of risk perception reported in this sample.
Food additive emulsifiers and risk of cardiovascular disease in the NutriNet-Santé cohort: prospective cohort study
Authors: Laury Sellem, Bernard Srour, Guillaume Javaux, Eloi Chazelas, Benoit Chassaing, Emilie Viennois, Charlotte Debras, Clara Salamé, Nathalie Druesne-Pecollo, Younes Esseddik, Fabien Szabo de Edelenyi, Cédric Agaësse, Alexandre De Sa, Rebecca Lutchia, Erwan Louveau, Inge Huybrechts, Fabrice Pierre, Xavier Coumoul, Léopold K Fezeu, Chantal Julia, Emmanuelle Kesse-Guyot, Benjamin Allès, Pilar Galan, Serge Hercberg, Mélanie Deschasaux-Tanguy, Mathilde Touvier
Journal: BMJ (2023)

Abstract Objective To assess the associations between exposure to food additive emulsifiers and risk of cardiovascular disease (CVD). Design Prospective cohort study. Setting French NutriNet-Santé study, 2009-21. Participants 95 442 adults (&gt;18 years) without prevalent CVD who completed at least three 24 hour dietary records during the first two years of follow-up. Main outcome measures Associations between intake of food additive emulsifiers (continuous (mg/day)) and risk of CVD, coronary heart disease, and cerebrovascular disease characterised using multivariable proportional hazard Cox models to compute hazard ratios for each additional standard deviation (SD) of emulsifier intake, along with 95% confidence intervals. Results Mean age was 43.1 (SD 14.5) years, and 79.0% (n=75 390) of participants were women. During follow-up (median 7.4 years), 1995 incident CVD, 1044 coronary heart disease, and 974 cerebrovascular disease events were diagnosed. Higher intake of celluloses (E460-E468) was found to be positively associated with higher risks of CVD (hazard ratio for an increase of 1 standard deviation 1.05, 95% confidence interval 1.02 to 1.09, P=0.003) and coronary heart disease (1.07, 1.02 to 1.12, P=0.004). Specifically, higher cellulose E460 intake was linked to higher risks of CVD (1.05, 1.01 to 1.09, P=0.007) and coronary heart disease (1.07, 1.02 to 1.12, P=0.005), and higher intake of carboxymethylcellulose (E466) was associated with higher risks of CVD (1.03, 1.01 to 1.05, P=0.004) and coronary heart disease (1.04, 1.02 to 1.06, P=0.001). Additionally, higher intakes of monoglycerides and diglycerides of fatty acids (E471 and E472) were associated with higher risks of all outcomes. Among these emulsifiers, lactic ester of monoglycerides and diglycerides of fatty acids (E472b) was associated with higher risks of CVD (1.06, 1.02 to 1.10, P=0.002) and cerebrovascular disease (1.11, 1.06 to 1.16, P&lt;0.001), and citric acid ester of monoglycerides and diglycerides of fatty acids (E472c) was associated with higher risks of CVD (1.04, 1.02 to 1.07, P=0.004) and coronary heart disease (1.06, 1.03 to 1.09, P&lt;0.001). High intake of trisodium phosphate (E339) was associated with an increased risk of coronary heart disease (1.06, 1.00 to 1.12, P=0.03). Sensitivity analyses showed consistent associations. Conclusion This study found positive associations between risk of CVD and intake of five individual and two groups of food additive emulsifiers widely used in industrial foods. Trial registration ClinicalTrials.gov NCT03335644 .